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Title: Caffeic acid phenethyl ester preferentially sensitizes CT26 colorectal adenocarcinoma to ionizing radiation without affecting bone marrow radioresponse

Abstract

Purpose: Caffeic acid phenethyl ester (CAPE), a component of propolis, was reported capable of depleting glutathione (GSH). We subsequently examined the radiosensitizing effect of CAPE and its toxicity. Methods and Materials: The effects of CAPE on GSH level, GSH metabolism enzyme activities, NF-{kappa}B activity, and radiosensitivity in mouse CT26 colorectal adenocarcinoma cells were determined. BALB/c mouse with CT26 cells implantation was used as a syngeneic in vivo model for evaluation of treatment and toxicity end points. Results: CAPE entered CT26 cells rapidly and depleted intracellular GSH in CT26 cells, but not in bone marrow cells. Pretreatment with nontoxic doses of CAPE significantly enhanced cell killing by ionizing radiation (IR) with sensitizer enhancement ratios up to 2.2. Pretreatment of CT26 cells with N-acetyl-L-cysteine reversed the GSH depletion activity and partially blocked the radiosensitizing effect of CAPE. CAPE treatment in CT26 cells increased glutathione peroxidase, decreased glutathione reductase, and did not affect glutathione S-transferase or {gamma}-glutamyl transpeptidase activity. Radiation activated NF-{kappa}B was reversed by CAPE pretreatment. In vivo study revealed that pretreatment with CAPE before IR resulted in greater inhibition of tumor growth and prolongation of survival in comparison with IR alone. Pretreatment with CAPE neither affected body weights nor produced hepatic,more » renal, or hematopoietic toxicity. Conclusions: CAPE sensitizes CT26 colorectal adenocarcinoma to IR, which may be via depleting GSH and inhibiting NF-{kappa}B activity, without toxicity to bone marrow, liver, and kidney.« less

Authors:
 [1];  [2];  [2];  [3];  [2];  [2];  [4];  [5];  [6]
  1. Department of Radiation Oncology, Mackay Memorial Hospital, Taipei, Taiwan (China)
  2. (China)
  3. Graduate Institute of Sport Coaching Science, Chinese Culture University, Taipei, Taiwan (China)
  4. Department of Pharmacology, National Research Institute of Chinese Medicine, Taipei, Taiwan (China)
  5. Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan (China)
  6. Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan (China). E-mail: msshiao@vghtpe.gov.tw
Publication Date:
OSTI Identifier:
20706273
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 63; Journal Issue: 4; Other Information: DOI: 10.1016/j.ijrobp.2005.08.001; PII: S0360-3016(05)02273-X; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; BONE MARROW; BONE MARROW CELLS; CARCINOMAS; CELL KILLING; CYSTEINE; ENZYME ACTIVITY; ESTERS; GLUTATHIONE; IN VIVO; INHIBITION; IONIZING RADIATIONS; KIDNEYS; LIVER; METABOLISM; MICE; PEROXIDASES; RADIATION DOSES; RADIOSENSITIVITY; SENSITIZERS; TOXICITY

Citation Formats

Chen, Y.-J., Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan, Graduate Institute of Sport Coaching Science, Chinese Culture University, Taipei, Taiwan, Liao, H.-F., Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan, Department of Molecular Biology and Biochemistry, National Chiayi University, Chiayi, Taiwan, Tsai, T.-H., Wang, S.-Y., and Shiao, M.-S.. Caffeic acid phenethyl ester preferentially sensitizes CT26 colorectal adenocarcinoma to ionizing radiation without affecting bone marrow radioresponse. United States: N. p., 2005. Web. doi:10.1016/j.ijrobp.2005.08.001.
Chen, Y.-J., Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan, Graduate Institute of Sport Coaching Science, Chinese Culture University, Taipei, Taiwan, Liao, H.-F., Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan, Department of Molecular Biology and Biochemistry, National Chiayi University, Chiayi, Taiwan, Tsai, T.-H., Wang, S.-Y., & Shiao, M.-S.. Caffeic acid phenethyl ester preferentially sensitizes CT26 colorectal adenocarcinoma to ionizing radiation without affecting bone marrow radioresponse. United States. doi:10.1016/j.ijrobp.2005.08.001.
Chen, Y.-J., Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan, Graduate Institute of Sport Coaching Science, Chinese Culture University, Taipei, Taiwan, Liao, H.-F., Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan, Department of Molecular Biology and Biochemistry, National Chiayi University, Chiayi, Taiwan, Tsai, T.-H., Wang, S.-Y., and Shiao, M.-S.. Tue . "Caffeic acid phenethyl ester preferentially sensitizes CT26 colorectal adenocarcinoma to ionizing radiation without affecting bone marrow radioresponse". United States. doi:10.1016/j.ijrobp.2005.08.001.
@article{osti_20706273,
title = {Caffeic acid phenethyl ester preferentially sensitizes CT26 colorectal adenocarcinoma to ionizing radiation without affecting bone marrow radioresponse},
author = {Chen, Y.-J. and Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan and Graduate Institute of Sport Coaching Science, Chinese Culture University, Taipei, Taiwan and Liao, H.-F. and Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan and Department of Molecular Biology and Biochemistry, National Chiayi University, Chiayi, Taiwan and Tsai, T.-H. and Wang, S.-Y. and Shiao, M.-S.},
abstractNote = {Purpose: Caffeic acid phenethyl ester (CAPE), a component of propolis, was reported capable of depleting glutathione (GSH). We subsequently examined the radiosensitizing effect of CAPE and its toxicity. Methods and Materials: The effects of CAPE on GSH level, GSH metabolism enzyme activities, NF-{kappa}B activity, and radiosensitivity in mouse CT26 colorectal adenocarcinoma cells were determined. BALB/c mouse with CT26 cells implantation was used as a syngeneic in vivo model for evaluation of treatment and toxicity end points. Results: CAPE entered CT26 cells rapidly and depleted intracellular GSH in CT26 cells, but not in bone marrow cells. Pretreatment with nontoxic doses of CAPE significantly enhanced cell killing by ionizing radiation (IR) with sensitizer enhancement ratios up to 2.2. Pretreatment of CT26 cells with N-acetyl-L-cysteine reversed the GSH depletion activity and partially blocked the radiosensitizing effect of CAPE. CAPE treatment in CT26 cells increased glutathione peroxidase, decreased glutathione reductase, and did not affect glutathione S-transferase or {gamma}-glutamyl transpeptidase activity. Radiation activated NF-{kappa}B was reversed by CAPE pretreatment. In vivo study revealed that pretreatment with CAPE before IR resulted in greater inhibition of tumor growth and prolongation of survival in comparison with IR alone. Pretreatment with CAPE neither affected body weights nor produced hepatic, renal, or hematopoietic toxicity. Conclusions: CAPE sensitizes CT26 colorectal adenocarcinoma to IR, which may be via depleting GSH and inhibiting NF-{kappa}B activity, without toxicity to bone marrow, liver, and kidney.},
doi = {10.1016/j.ijrobp.2005.08.001},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 4,
volume = 63,
place = {United States},
year = {Tue Nov 15 00:00:00 EST 2005},
month = {Tue Nov 15 00:00:00 EST 2005}
}
  • All-trans retinoic acid (ATRA) induces complete remission in a high proportion of patients with acute promyelocytic leukemia (APL); however, the response is sometimes very slow. Furthermore, relapse and resistance to treatment often occur despite continued treatment with ATRA. Thereafter, combination treatment strategies have been suggested to circumvent these problems. The present study demonstrates that caffeic acid phenethyl ester (CAPE), a major component of honeybee propolis, enhanced ATRA-induced granulocytic differentiation in HL-60, a human promyelocytic cell line. The differentiation was assessed by Wright-Giemsa stain, nitroblue tetrazolium reduction, and membrane differentiation marker CD11b. In addition, CAPE enhanced ATRA-induced cell cycle arrest atmore » the G1 phase by decreasing the association of cdk2-cyclin E complex. Finally, it was demonstrated that CAPE promoted the ATRA-mediated nuclear transcription activation of RAR{alpha} assessed by EMSA assay and enhanced the expression of target genes including RAR{alpha}, C/EBP{epsilon}, and p21 protein resulting in the differentiation development of leukemia. It is suggested that CAPE possesses the potential to enhance the efficiency of ATRA in the differentiation therapy of APL.« less
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